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He will semi-randomly switch between hopping towards the player, spitting a burst of blood shots (telegraphed by smiling), or launch into the air and land at the spot the player was standing in when he went up along with blood shots fired in every direction when he hits the ground.

The distance between Isaac and Monstro will not influence the attack he'll choose, he switches between them at will. Therefore, you'll want to stay at medium range to retain maximum flexibility. The blood shot spray looks nasty, but the shots have arcs that often go over your head.

It's also possible to circle around Monstro while staying at a short distance. This way, you don't have to worry about his shots, but his small leaps become a bit more dangerous.

Despite his bulk, Monstro moves around a fair bit; area of effect items (like Mr. Boom, Lemon Mishap, or Doctor's Remote) will not be very effective unless you get lucky on placement. Doctor's Remote, however, works somewhat well as you can use mouse clicks to stay on target with Monstro. Try to wait until he launches into the air, then move and aim where you were standing when he lept. Use his shadow to track where he will land.

Regular bombs take large chunks out of his health, but if he decides to launch you may end up wasting the bomb. An easy way to use area of effect items is when Monstro makes a huge jump, he will land approximately at your last position before he jumped, so just use the item before moving.

If you're down to one heart, avoiding damage becomes a number-one priority as some of his shots (the bigger ones) can deal up to a full heart of damage.

For some people it's hard to tell where he is when jumping in the air, so homing shots can help to predict his landing. You can sometimes tell by the shadow that his body makes in where he will land, but mainly, he only lands where your current position was/is

It's possible to run underneath Monstro while he is "hopping". This can make shooting a bit easier.

Pay attention. If Monstro uses his blood spray while you are cornered, look for an opening. There's an opening in every barrage he throws at you, so use this to your advantage.

This version is much smaller and has less health. An additional Monstro shows up, and you'll have to battle both of them simultaneously. In boss rooms, there will be two and in normal rooms in later levels, one will be added to the amount that would spawn in the room by default. Obviously, when smaller, it's harder to stay still and maintain fire, and with two or three of them present, it's best to run in a circle around them and never fully stop moving unless they're both just hopping around.